10th Anniversary of Antibiotics—Recent Advances in Bacteriophage Therapy

A special issue of Antibiotics (ISSN 2079-6382). This special issue belongs to the section "Bacteriophages".

Deadline for manuscript submissions: closed (31 December 2021) | Viewed by 13781

Special Issue Editor

Departamento de Biologia, CESAM - Centro de Estudos do Ambiente e do Mar, Campus Universitário de Santiago, Universidade de Aveiro, 3810-193 Aveiro, Portugal
Interests: phage therapy; antimicrobial photodynamic therapy; alternative approaches to antibiotics
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Special Issue Information

Dear Colleagues,

Phage therapy is not a new practice, as phages have been used since the end of the nineteenth century. Right after their discovery, however, with the progressive production and mass use of antibiotics, research about the therapeutic potential of bacteriophages was gradually neglected, especially in Western contries. Due to the increase in antibiotic resistance, in recent years the need to find new antimicrobial alternatives has led to a rediscovery of bacteriophages all around the world. Although recent research has shown that bacteriophages can represent a viable alternative or be part of conventional antimicrobial therapy in combination with antibiotics or other molecules/therapies, in clinical and non-clinical areas more studies are needed. In vivo/ex vivo experiments directed at multidrug-resistant bacteria, intracellular bacteria, bacteria capable of forming biofilms, bacteria involved in chronic infections; the prevention of phage-resistance mechanisms by bacteria; the impact of phage use on the environment; legislation development for phage application are among the phage therapy areas that deserve further study.

The Antibiotics journal was founded in 2012 and, during the past 10 years, has launched more than 100 Special Issues and published more than 1500 papers. The journal covers all aspects of antibiotic discovery, use and preservation. The year 2021 marks the 10th anniversary of Antibiotics, which we are excited to celebrate with a Special Issue.

This Special Issue welcomes both research and review papers on the most recent and innovative developments in phage therapy bacteriophages. We hope that the Special Issue can further encourage and promote the scientific contributions of the researchers in this field, highlighting the advances in phage therapy in both clinical and nonclinical areas, namely:

  • Phage therapy against multidrug-resistant bacteria, intracellular bacteria, bacteria capable of forming biofilms, and bacteria involved in chronic infections;
  • The impact of phage use on the environment;
  • The effects of environmental factors on phage viability;
  • The functional stabilization/preservation of phage particles;
  • Phage administration routes, phage concentrations, and moments of treatment;
  • Phage specificity to target bacteria;
  • The development of phage-resistant bacteria;
  • Phage therapy combined with other antimicrobial approaches;
  • Phage therapy regulatory options for the way forward.

Prof. Dr. Adelaide Almeida
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Antibiotics is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • bacteriophages
  • phage therapy
  • pathogenic bacteria
  • alternative approaches
  • combined therapy
  • phage-resistance
  • regulations
  • environment implications

Published Papers (4 papers)

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16 pages, 1879 KiB  
Article
Campylobacter Bacteriophage Cocktail Design Based on an Advanced Selection Scheme
by Severin Michael Steffan, Golshan Shakeri, Corinna Kehrenberg, Elisa Peh, Manfred Rohde, Madeleine Plötz and Sophie Kittler
Antibiotics 2022, 11(2), 228; https://doi.org/10.3390/antibiotics11020228 - 10 Feb 2022
Cited by 6 | Viewed by 1872
Abstract
Campylobacteriosis is a worldwide-occurring disease and has been the most commonly reported zoonotic gastrointestinal infection in the European Union in recent years. The development of successful phage-based intervention strategies will require a better understanding of phage–bacteria interactions to facilitate advances in phage cocktail [...] Read more.
Campylobacteriosis is a worldwide-occurring disease and has been the most commonly reported zoonotic gastrointestinal infection in the European Union in recent years. The development of successful phage-based intervention strategies will require a better understanding of phage–bacteria interactions to facilitate advances in phage cocktail design. Therefore, this study aimed to investigate the effects of newly isolated group II and group III phages and their combinations on current Campylobacter field strains. A continuous workflow for host range and efficiency of plating (EOP) value determination was combined with a qPCR-based phage group identification and a liquid-based planktonic killing assay (PKA). An advanced analysis scheme allowed us to evaluate phage cocktails by their efficacy in inhibiting bacterial population growth and the resulting phage concentrations. The results of this study indicate that data obtained from PKAs are more accurate than host range data based on plaque formation (EOP). Planktonic killing assays with Campylobacter appear to be a useful tool for a straightforward cocktail design. Results show that a group II phage vB_CcM-LmqsCP218-2c2 and group III phage vB_CjM-LmqsCP1-1 mixture would be most promising for practical applications against Campylobacter coli and Campylobacter jejuni. Full article
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14 pages, 2736 KiB  
Article
Combined Effect of Phage phT4A and Pressure-Based Strategies in the Inhibition of Escherichia coli
by Carla Pereira, João F. Marques, Sílvia Reis, Pedro Costa, Ana P. Martins, Carlos A. Pinto, Jorge A. Saraiva and Adelaide Almeida
Antibiotics 2022, 11(2), 211; https://doi.org/10.3390/antibiotics11020211 - 07 Feb 2022
Cited by 1 | Viewed by 1563
Abstract
The major concern regarding the bacteriophage (or phage) therapy approach is the regrowth of bacteria after treatment, a consequence of the emergence of phage-resistant mutants. However, this limitation can be overcome by combining different therapies. In this study, the potential of combining phage [...] Read more.
The major concern regarding the bacteriophage (or phage) therapy approach is the regrowth of bacteria after treatment, a consequence of the emergence of phage-resistant mutants. However, this limitation can be overcome by combining different therapies. In this study, the potential of combining phage phT4A with pressure storage (HS) to enhance the control of Escherichia coli and bacterial regrowth after treatment was evaluated. For that, the combining effect of phage phT4A and HS was studied and compared with storage at atmospheric pressure (AP) under refrigeration (4 °C, RF) and room temperature (RT). Initially, the effect of high hydrostatic pressure (200, 300 and 400 MPa) and HS (75 MPa), as well as refrigeration in phage phT4A viability, was determined. However, a considerable phage inactivation was verified at 200 MPa and so only HS at 75 MPa was further studied for combined treatment. The combined treatment with phage phT4A and HS was more efficient (reduction of 2.5 log CFU/mL after 7 days of storage) than phage phT4A (E. coli concentration was similar to that of the bacterial control after 7 days of storage) and HS (reduction of 1.8 log CFU/mL after 7 days of storage) applied individually. The combination of phage phT4A with refrigerated storage did not decrease E. coli levels. However, both the combination of phage with HS and the treatment with HS at 75 MPa effectively reduced E. coli concentration and prevented its regrowth. Phage phT4A viability was slightly affected during HS; however, the efficiency of the combined treatment phage-HS was not compromised. Further studies are needed to validate these findings in food products. Full article
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18 pages, 7919 KiB  
Article
Topically Applied Bacteriophage to Control Multi-Drug Resistant Klebsiella pneumoniae Infected Wound in a Rat Model
by Mohamed S. Fayez, Toka A. Hakim, Mona M. Agwa, Mohamed Abdelmoteleb, Rania G. Aly, Nada N. Montaser, Abdallah S. Abdelsattar, Nouran Rezk and Ayman El-Shibiny
Antibiotics 2021, 10(9), 1048; https://doi.org/10.3390/antibiotics10091048 - 27 Aug 2021
Cited by 25 | Viewed by 5775
Abstract
(Background): Multi-drug-resistant Klebsiella pneumoniae (MDR-KP) has steadily grown beyond antibiotic control. Wound infection kills many patients each year, due to the entry of multi-drug resistant (MDR) bacterial pathogens into the skin gaps. However, a bacteriophage (phage) is considered to be a potential antibiotic [...] Read more.
(Background): Multi-drug-resistant Klebsiella pneumoniae (MDR-KP) has steadily grown beyond antibiotic control. Wound infection kills many patients each year, due to the entry of multi-drug resistant (MDR) bacterial pathogens into the skin gaps. However, a bacteriophage (phage) is considered to be a potential antibiotic alternative for treating bacterial infections. This research aims at isolating and characterizing a specific phage and evaluate its topical activity against MDR-KP isolated from infected wounds. (Methods): A lytic phage ZCKP8 was isolated by using a clinical isolate KP/15 as a host strain then characterized. Additionally, phage was assessed for its in vitro host range, temperature, ultraviolet (UV), and pH sensitivity. The therapeutic efficiency of phage suspension and a phage-impeded gel vehicle were assessed in vivo against a K. pneumoniae infected wound on a rat model. (Result): The phage produced a clear plaque and was classified as Siphoviridae. The phage inhibited KP/15 growth in vitro in a dose-dependent pattern and it was found to resist high temperature (˂70 °C) and was primarily active at pH 5; moreover, it showed UV stability for 45 min. Phage-treated K. pneumoniae inoculated wounds showed the highest healing efficiency by lowering the infection. The quality of the regenerated skin was evidenced via histological examination compared to the untreated control group. (Conclusions): This research represents the evidence of effective phage therapy against MDR-KP. Full article
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9 pages, 1133 KiB  
Brief Report
Synergy between Phage Sb-1 and Oxacillin against Methicillin-Resistant Staphylococcus aureus
by Kevin Simon, Wolfgang Pier, Alex Krüttgen and Hans-Peter Horz
Antibiotics 2021, 10(7), 849; https://doi.org/10.3390/antibiotics10070849 - 13 Jul 2021
Cited by 15 | Viewed by 3110
Abstract
Methicillin-resistant Staphylococcus aureus (MRSA) is a notorious pathogen responsible for not only a number of difficult-to-treat hospital-acquired infections, but also for infections that are community- or livestock-acquired. The increasing lack of efficient antibiotics has renewed the interest in lytic bacteriophages (briefly phages) as [...] Read more.
Methicillin-resistant Staphylococcus aureus (MRSA) is a notorious pathogen responsible for not only a number of difficult-to-treat hospital-acquired infections, but also for infections that are community- or livestock-acquired. The increasing lack of efficient antibiotics has renewed the interest in lytic bacteriophages (briefly phages) as additional antimicrobials against multi-drug resistant bacteria, including MRSA. The aim of this study was to test the hypothesis that a combination of the well-known and strictly lytic S. aureus phage Sb-1 and oxacillin, which as sole agent is ineffective against MRSA, exerts a significantly stronger bacterial reduction than either antimicrobial alone. Eighteen different MRSA isolates and, for comparison, five MSSA and four reference strains were included in this study. The bacteria were challenged with a combination of varying dosages of the phage and the antibiotic in liquid medium using five different antibiotic levels and four different viral titers (i.e., multiplicity of infections (MOIs) ranging from 10−5 to 10). The dynamics of the cell density changes were determined via time-kill assays over 16 h. Positive interactions between both antimicrobials in the form of facilitation, additive effects, or synergism were observed for most S. aureus isolates. These enhanced antibacterial effects were robust with phage MOIs of 10−1 and 10 irrespective of the antibiotic concentrations, ranging from 5 to 100 µg/mL. Neutral effects between both antimicrobials were seen only with few isolates. Importantly, antagonism was a rare exception. As a conclusion, phage Sb-1 and oxacillin constitute a robust heterologous antimicrobial pair which extends the efficacy of a phage-only approach for controlling MRSA. Full article
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